There is convincing evidence that Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disease (PTLD). Primary EBV infection following transplantation occurs in as many as 90% of cases of PTLD in children and pretransplant EBV seronegativity is a recognized risk factor for developing PTLD. Other risk factors include young age at the time of transplant, the type of transplant that the recipient receives and the type and intensity of immunosuppression. The clinical presentation is often nonspecific and tissue biopsy is necessary to establish the diagnosis. There appears to be a correlation between PTLD and EBV viral load measured by polymerase chain reaction (PCR) of the peripheral blood and quantitative PCR may be a useful guide in the management of PTLD. Antiviral drugs and cytomegalovirus-immunoglobulin G may have a role in preventing PTLD. Because PTLD results from functional over-immunosuppression, the initial treatment is reduction of immunosuppression. Antiviral agents, interferon, immuno-based monoclonal therapy, cell-based therapy and chemotherapy also have a potential role in treating this disorder. At the present time there is no standardized approach to the evaluation and treatment of PTLD.